The functional relationship between the ets gene of transforming leukemia virus, E26, and its cellular prototypes has been facilitated by structural comparisons at the nucleic acid and predicted protein levels. The genomic structure of the human and mouse Ets-1 and Ets-2 genes has been characterized. In addition, sequence analyses of the human and mouse Ets- 1 promoters and the 3' non-coding regions of the human and mouse Ets-2 cDNAs has been accomplished. Sequence alignment of the human and mouse Ets-1 genes has allowed identification of highly-conserved 5' and 3' nucleic acid sequences. Oligonucleotides containing the 5' conserved sequences have been used to identify nuclear binding proteins. Genes in addition to ETS1, ETS2, ERG, ELK1 and ELK2 are present in the human genome. Thus far, two loci that appear to represent ETS2 pseudogenes have been defined and a new gene designated ERGB that, although related to ERG at the nucleotide level, has unique properties, including novel chromosome location and a more ubiquitous pattern of gene expression. Like ETS1, the ERGB gene is located on chromosome 11, and is found on the 4q- chromosome resulting from the translocation t(4;11). It has been demonstrated that ERGB protein can act as a transcriptional activator.